In general, it is preferable that medicines are easy to swallow and in the administrational form of small volume or quantity. In addition, it is desirable that their ingredients are uniformly distributed and they are administered efficiently, e.g., in a high concentration. Encapsulation can satisfy such purposes as discussed in a Japanese patent application titled "Simplified Encapsulation of Medicines," which has been published in the Japanese Unexamined Patent Gazette No. 1-502185.
This Gazette discloses a specific solvent solution system that is to be encapsulated and composed of an ionizable medicine, hydroxide ions or hydrogen ions enough to enhance the solubility of said medicine, and a specified amount of water and polyethylene glycol (PEG).
However, this solvent system using PEG can cause a local reaction due to existing hydroxide ions depending on the properties of other components in the capsule. As the result, an ester may be produced and, thereby, may cause the purity of the encapsulated contents to be lowered.
The inventors of the present invention have earnestly investigated the purity deterioration of the solute component (medicine) due to its reaction with the solvent and found that polyoxyethylene sorbitan fatty acid ester (hereafter, abbreviated POSE) is a solvent useful for preventing the deterioration of purity, and have reached the present invention.
1. Field of the Invention
The present invention relates to a solvent system that includes a highly concentrated acidic medicine, the solubility of which is enhanced by partial ionization of said medicine.
This solvent system is used by being enclosed in soft gels (soft elastic gelatin capsules) or hard gelatin shells.
2. Outline of the Invention
The present invention relates to a high concentration solvent system to be enclosed in capsules, said system being composed of
a) 10-80% by weight acidic medicine, PA1 b) 0.1-1.0 mole hydroxide ions for one mole of said medicine, and PA1 c) 1-20% by weight water PA1 a) Ibuprofen, Naproxen, Indomethacin, Acetaminophen, etc. may be exemplified as among the acidic medicines to be used in this invention. PA1 b) In the present invention, about 0.1-1.0 mole hydroxide ions is used for each molar equivalent of said acidic medicine. PA1 c) in the present invention, about 1-20% by weight water is included in POSE. If the water content is lower than about 1% by weight, the ionization of the acidic medicine might be incomplete though it depends on the nature of the medicine used, making the desired solubility unattainable. On the other hand, if the water content is more than about 20% by weight, the capsule containing such water may be softened and impractical. PA1 TWEEN 20 ethylene oxide condensate of sorbitanmonolaurate PA1 TWEEN 21 ethylene oxide condensate of sorbitanmonolaurate PA1 TWEEN 40 ethylene oxide condensate of sorbitanmonopalmitate PA1 TWEEN 60 ethylene oxide condensate of sorbitanmonostearate PA1 TWEEN 61 ethylene oxide condensate of sorbitanmonostearate PA1 TWEEN 65 ethylene oxide condensate of sorbitantristearate PA1 TWEEN 80 ethylene oxide condensate of sorbitanmonooleate PA1 TWEEN 81 ethylene oxide condensate of sorbitanmonooleate PA1 TWEEN 85 ethylene oxide condensate of sorbitantrioleate PA1 a) The solubility of acidic medicine can be increased by about 4-400%. PA1 b) The chemical stability of the included medicine is higher than that in the case where PEG is used as the primary solvent. PA1 c) When filled in capsules, the capsule contents can be reduced in volume. PA1 d) No deteriorative effects are inflicted on the shell of capsules.
included in POSE, the mean molecular weight of said POSE being 600-3000.